BACKGROUND: By 2015, the emergence and dissemination of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion threatened regional and global malaria control efforts. In response, Greater Mekong Subregion countries committed to malaria elimination by 2030, with strengthened surveillance as a strategic pillar. In 2017, Cambodia introduced an elimination-oriented digital Malaria Information System (MIS). Its health center app enables real-time, geo-located, case-based malaria reporting across primary health centers, and is fully integrated with the MIS. OBJECTIVE: This study aimed to evaluate the real-world national implementation of Cambodia's Android-based health center app, considering coverage, fidelity, timeliness, and data use, and their effects on malaria surveillance performance, case management, programmatic response, and public health outcomes. METHODS: System performance and public health use were assessed using system-generated metadata, national surveillance data, and user surveys. Operational indicators included technical performance, data completeness, and reporting timeliness, alongside surveillance outcomes such as case notification, classification, reactive case detection, and foci investigation. Nationwide user experience was measured via a survey of 761 health centers across 21 provinces, with in-depth structured surveys at 9 health centers in 3 provinces. Descriptive analyses evaluated system functionality, contribution to malaria surveillance and response, and usability among frontline health workers. RESULTS: The health center app demonstrated strong technical performance, with rapid loading and resilient data transmission under low-bandwidth conditions, supporting reliable reporting in resource-constrained settings. Integrated real-time dashboards provided analytics for case management, surveillance monitoring, risk stratification, and targeted public health interventions. Data completeness remained high (99%, 89/90 fields in 2024), demonstrating consistent routine use even as case incidence declined. Between January 1, 2025, and July 31, 2025, 69 malaria cases were reported nationally (23 locally acquired, 7 domestically imported, and 39 internationally imported). Of these, 95.7% (66/69) were notified and classified within 1 day. Reactive case detection was completed within 3 days for all 21 eligible cases, and 16 of 19 eligible foci received a response within 7 days, indicating strong operational responsiveness. User surveys showed 96.3% (733/761) of health centers were satisfied or very satisfied, 90.1% (686/761) reported rare or no technical issues, and 91.7% (698/761) found the app easy to navigate. Operational challenges included limited internet connectivity, transport to remote areas, and electricity interruptions. In-depth surveys confirmed high uptake, confidence in reporting, and routine use of surveillance data, although gaps in local analytical capacity were identified. CONCLUSIONS: Developed and managed locally to enhance sustainability, the MIS drove significant reductions in malaria case incidence, with the health center app contributing timely, complete, structured reporting at the point of care. Public health responses were facilitated by real-time analysis, targeted interventions, and decentralized decision-making. User engagement was sustained as malaria cases declined, and further enhancements are planned to ensure seamless transition to postelimination surveillance, reducing the risk of malaria reestablishment in Cambodia.